The Influence of Ventilation Measures on the Airborne Risk of Infection in Schools: A Scoping Review

Objectives: To review the risk of airborne infections in schools and evaluate the effect of intervention measures reported in field studies. Background: Schools are part of a country’s critical infrastructure. Good infection prevention measures are essential for reducing the risk of infection in schools as much as possible, since these are places where many individuals spend a great deal of time together every weekday in a small area where airborne pathogens can spread quickly. Appropriate ventilation can reduce the indoor concentration of airborne pathogens and reduce the risk of infection. Methods: A systematic search of the literature was conducted in the databases Embase, MEDLINE, and ScienceDirect using keywords such as school, classroom, ventilation, carbon dioxide (CO2) concentration, SARS-CoV-2, and airborne transmission. The primary endpoint of the studies selected was the risk of airborne infection or CO2 concentration as a surrogate parameter. Studies were grouped according to the study type. Results: We identified 30 studies that met the inclusion criteria, six of them intervention studies. When specific ventilation strategies were lacking in schools being investigated, CO2 concentrations were often above the recommended maximum values. Improving ventilation lowered the CO2 concentration, resulting in a lower risk of airborne infections. Conclusions: The ventilation in many schools is not adequate to guarantee good indoor air quality. Ventilation is an important measure for reducing the risk of airborne infections in schools. The most important effect is to reduce the time of residence of pathogens in the classrooms.


Introduction
In Germany, there are about 32,228 schools, around half of them primary schools. During the 2020/2021 school year, 790,608 teachers taught about 8.38 million students at general education schools [1]. Many individuals of different age groups spend several hours together every weekday in relatively small areas in educational facilities. In connection with the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2)-the cause of COVID-19 that was declared a pandemic by the WHO on 11 March 2020 [2]-schools attracted attention as potential hotspots for the transmission of SARS-CoV-2. As a result, schools in Germany were closed in March 2020 as part of a nationwide lockdown to reduce the further spread of SARS-CoV-2 and the infection of families [3]. Certainly, these measures prevented many infections. However, there were various side effects, such as deterioration in school performance, psychological and physiological illness, and violence in homes, not to mention economic costs, which will need to be prevented in the future [4][5][6][7]. SARS-CoV-2 is transmitted primarily via infectious droplets and aerosols produced when speaking, breathing, coughing, and sneezing [8][9][10][11][12]. As far as is known, contact transmission, by means of contaminated surfaces or objects, plays only a minor role [13]. Aerosols spread in a room and can persist for longer periods, especially when air exchange is limited. They remain potentially infectious so that there is also a more widespread risk of infection in the far field (more than 1.5 m from an infectious person). In the case of droplet infection, on the other hand, transmission tends to take place between individuals in closer proximity, in the near field (in a radius of about 1.5 m from an infectious person). Airborne infections through droplets and aerosols can, however, merge so that a strict distinction is either difficult to make or is not useful [14].
There are other pathogens that are not as well known to the public but which can also lead to local outbreaks in a school setting. Important examples are respiratory pathogens such as the influenza virus [15,16], the measles virus [17], or the mycobacterium tuberculosis [18].
Improving ventilation can reduce the transmission of airborne pathogens by diluting or eliminating pathogens [11,19]. The ventilation can be natural ventilation (NV), for example through windows/doors, or mechanical ventilation (MV), for example by heating, ventilation, and air conditioning (HVAC) systems. A combination of NV and MV in the form of hybrid ventilation is also possible [20]. Most European schools are ventilated by natural ventilation without a defined ventilation rate [21,22].
Carbon dioxide (CO 2 ) is exhaled together with droplets/particles that can contain virus. Indoor CO 2 concentration is often used as an indicator of indoor air quality (IAQ) and the available ventilation rate per person [23], and is therefore often used as a surrogate parameter for the risk of infection or transmission of SARS-CoV-2 or other airborne infectious pathogens [24][25][26]. In Germany, indoor CO 2 concentrations below 1000 ppm are classified as harmless, concentrations between 1000 and 2000 ppm as conspicuous, and concentrations over 2000 ppm as unacceptable [27]. It is possible that revised CO 2 limit values are necessary, related to activity levels [26]. Originally, von Pettenkofer proposed the reference value of 1000 ppm as the upper limit for CO 2 concentration indoors [28]. When proposing this reference value, he intended primarily to prevent students from having problems concentrating because of excessive concentrations of CO 2 . It is relatively easy and comparatively cheap to measure CO 2 concentration using CO 2 measurement equipment.
There are some limitations to using the CO 2 concentration as a surrogate parameter for the risk of infection: after a certain amount of time, it reaches a steady state, whereas the number of particles containing virus that are inhaled by a person in the room increases over time even if the concentration of particles in the room remains unchanged. Kriegel et al. postulate that the CO 2 dose (ppm*h) might be more meaningful than the CO 2 concentration when estimating the risk of infection [29].
After more than 2.5 years of pandemic experience we want to examine, on the basis of published field studies, whether and to what extent interventions in relation to ventilation measures in schools have contributed to reducing the risk of airborne infection or to CO 2 concentration, the surrogate endpoint. Additional measures such as masks, regular testing, vaccinations, etc., which can also reduce the risk of infection, were not investigated [16,[30][31][32][33].

Search Strategy
Systematic searches of the literature in the databases Embase, MEDLINE, and Sci-enceDirect were carried out by two persons between 9 July 2021 and 6 May 2022. Publications in English or German, with a publication date previous to 1 May 2022 were considered. To identify relevant studies in the literature, a combination of the following keywords was used: "school", "classroom", "child", "student", "pupil", "ventilation", "CO 2 ", "air filtration", "indoor air quality", "architecture", "building", "COVID-19", "SARS-CoV-2", "measles", "respiratory syncytial virus", "infection", "prevention", and "airborne transmission". In addition, we considered relevant publications found during the study of publications identified earlier. The program Endnote was used for reference management and the elimination of duplicates.

Inclusion and Exclusion Criteria
Studies were included that were carried out in classrooms or school buildings with the primary endpoint CO 2 concentration or the risk of infection/transmission of various airborne pathogens (e.g., SARS-CoV-2, measles, influenza) or infection from these airborne pathogens in relation to ventilation or building-associated factors. "School" here, depending on the country where a study was carried out, refers to K-12 schools or pre-schools, or primary and secondary schools. Colleges and universities, frequently with larger classroom designs, are not considered. In addition, only studies carried out in high and middleincome countries in climate zones comparable to Germany's were included in order to ensure comparability and transferability. Regarding the study design, intervention studies, observational studies, and mathematical modeling studies were included. In the course of the writing this article, a new study was published that was highly relevant to the question being investigated [34]. This study was also included, although its publication date was later than the period used in literature search.
There was a great deal of overlap among studies carried out before the pandemic which examined the effects of CO 2 in classrooms, e.g., as a surrogate parameter for the occurrence of concentration disorders. Hence, observational and mathematical modeling studies published before 2020, in which CO 2 concentration was not associated with the transmission of airborne infections as their primary endpoint, were excluded.

Study Selection and Structuring
In selecting studies, after duplicates were eliminated, studies were screened by title and abstract. The remaining studies were then read in full and checked for relevance. A flowchart depicting the process of study selection is shown in Figure 1.  Figure 1. Flowchart of study selection process.

Results
We identified 30 studies that met the inclusion criteria ( Figure 1). Of these, six were intervention studies whose primary endpoint was CO 2 concentration or SARS-CoV-2 infection in clusters of cases (Table 1), 16 were observational studies, some with additional mathematical modeling, and eight were mathematical modeling studies whose primary endpoints were CO 2 concentration or infection by/transmission of various respiratory pathogens, e.g., SARS-CoV-2, measles, and influenza ( Table 2).
In summary, in many classrooms, CO 2 concentrations were higher than 1000 ppm and ventilation could lower CO 2 concentrations [24,[34][35][36][37][38]. Nevertheless, even this step was sometimes not adequate to keep CO 2 concentrations below 1000 ppm permanently, especially when individuals were present in the room during the ventilation period [39]. As shown in other studies [40][41][42][43], CO 2 concentrations in classrooms with mechanical ventilation were lower than in those naturally ventilated. For example, Vassella et al. found the median CO 2 concentration in MV classrooms was 686-1320 ppm, whereas in NV classrooms it was 862-2898 ppm [38]. In one intervention study, the authors found that in mechanically ventilated classrooms, the relative risk of infection with SARS-CoV-2 was reduced by at least 74% compared with those naturally ventilated. At higher ventilation rates of > 10 L s −1 student −1 , the relative risk of infection decreased by at least 80%. The protective effect of MV was greater in periods of higher regional incidence of SARS-CoV-2 [34].
Some building-associated factors can influence the efficiency of ventilation and the risk of infection by airborne pathogens. Room size affected the risk of infection, to a particular degree in small, poorly ventilated rooms [22,44]. Stein-Zamir et al. describe a major SARS-CoV-2 outbreak triggered by two index cases. In the school in question, classrooms were overcrowded (1.1-1.3 m 2 per person). The requirement to wear masks had nonetheless been abolished and contacts between students also existed outside the school setting, possibly leading to infections outside the school [45]. A visual feedback system that monitored CO 2 concentrations and indicated the need for ventilation could achieve a considerable reduction in CO 2 concentrations through increased NV as compared to the control group without a visual feedback system [35]. Note: NV = natural ventilation; MV = mechanical ventilation/mechanically ventilated; MVS = mechanical ventilation system; SD = standard deviation; CO 2 conc. = CO 2 concentration; RR = relative risk; RRR = relative risk reduction; IP = incidence proportion; IPR = incidence proportion ratio. (1) and (2)  (2) Lower indoor temperature, more frequent thermal discomfort [52] Observational study, outbreak analysis 1 secondary school, Germany, 2020 Analysis of an outbreak after schools reopened after the first lockdown. Examination of causes and course (clinical, contact, laboratory data, WGS analysis). Students did not wear masks, teachers sometimes wore masks.

SARS-CoV-2 infection
A teacher was identified as the index case, subsequently 31 students, 2 teachers and 3 household contacts were infected. Most infections were in connection with 2 lessons of the index case (1 building, rooms of possible transmission were all located on two floors). Limited ventilation, narrow sanitary facilities, 1 crowded classroom. [17] Observational study, outbreak analysis 1 elementary school, upstate New York, USA, 1974 Analysis of a large measles outbreak, investigation of the impact of vaccination and ventilation. School equipped with 2 ventilation systems. Air is recirculated after filtration.

Measles Infection
97% of the children were vaccinated. Index case infected 28 other students, 60 children were subsequently infected. Recirculation of the virus by the ventilation system augmented transmission. The most important exposure sites were the same classroom as the infector(s), another classroom that used the same ventilation system, and school buses.   (2). Variations of secondary infections between the classrooms, even those using the same ventilation system. [54] (

SARS-CoV-2 infection
35% lower incidence when schools improved their ventilation strategies, 48% reduction with combination of increased NV and air filtration/purification and 37% reduction when students and staff wore face masks.

Measles transmission risk
Transmission risk 74 times higher for unvaccinated students, higher in high schools than in elementary schools (median 5.8% and 3.8% respectively). Schools with ductless systems without air filters have the highest transmission risk (median 6.0%), schools with ductless systems with air filters have the lowest (median: 3.7%). Using a better filter reduced transmission risk for unvaccinated students (45% for MERV8, 32% for MERV13, and 29% for HEPA filter, median values). Increasing ventilation rates decreased transmission risk for unvaccinated students (46% basic control scenario, 38% regular, 33% advanced infection control scenario).

Discussion
Improving ventilation in classrooms by means of mechanical or natural ventilation decreased CO 2 concentrations and thus the assumed risk of infection [24,34,35,37,38]. In some studies, however, CO 2 concentrations were still above the recommended upper limit of 1000 ppm [37]. Despite the large number of studies found in the literature search, only six intervention studies were identified that met the inclusion criteria. In addition, the studies were very heterogeneous with regard to the building architecture (size of the classrooms, number, size, arrangement and orientation of the windows, etc.) and setting (country, season). In some studies, several infection prevention measures were applied simultaneously, which complicated a determination of the extent of the effect of a specific measure.
The literature search did not enable us to define maximum acceptable values for CO 2 concentration. However, because it is often recommended by other authors and organizations [63][64][65], we postulate that the indoor CO 2 concentration should not exceed 1000 ppm on average over time in all classrooms. During a pandemic involving an airborne pathogen, it should not exceed 800 ppm on average over time, although CO 2 concentrations up to 1000 ppm for short periods are tolerable. This can be implemented using mechanical ventilation, for example, using HVAC systems, or by NV with windows and doors [66]. Our literature search confirms earlier findings that mechanically ventilated classrooms have significantly higher ventilation rates than naturally ventilated ones [40][41][42][43]. Thus, we also conclude that classrooms should be equipped with an MV system, since mechanically ventilated classrooms appear to have lower, more stable mean CO 2 concentrations than naturally ventilated ones. Hence, a reduction of aerosols that could contain virus can be more easily achieved, which would result in a reduction of the risk of infection [30,34,38,46]. In one study, it was shown that a 74% reduction of the relative risk of infection could be achieved in classrooms with MV systems, and that for each additional unit in the ventilation rate per student, the relative risk reduction ranged from 12-15% [34]. The ventilation rates need to be adjusted depending on the age, activity, and number of individuals in the room. There are other positive effects of HVAC systems, such as indoor temperature regulation, which may prevent school closures due to extremely high temperatures. Birmili et al. found that, especially with extremely low or high outdoor temperatures, HVAC systems can prevent thermal discomfort [14]. Moreover, the elimination of CO 2 and other possible pollutants may improve students' ability to concentrate [67,68]. Installation or retrofitting of HVAC systems should be standard in schools. Until this is implemented, rooms should have a sufficient number of windows to enable large-area natural ventilation by means of a standardized ventilation regime.
Miranda et al. found that a strong NV regime could keep the average CO 2 concentrations at low levels between 450 and 650 ppm in university classrooms. However, the significant drop in indoor temperature led to thermal dissatisfaction [69]. Rooms that cannot be ventilated either naturally or mechanically are not suitable for school lessons. Like other authors [70,71] and organizations [72], we recommend installing CO 2 measuring devices with clearly visible displays or sound alarms in classrooms. Such equipment indicates when ventilation is needed and helps to check the success of the ventilation. Several studies showed that CO 2 concentration could be decreased dramatically using NV if CO 2 measuring devices that visualized the effect of ventilation monitored CO 2 concentration [24,35,37]. Laurent and Frans found that the use of CO 2 measuring devices in a hospital resulted in significantly shorter periods of time with CO 2 concentrations above 1000 ppm and lower overall maximum values [73]. A visual feedback system makes it easy to recognize when ventilation is necessary [35]. The REHVA recommends using CO 2 monitors with red, yellow, and green indicator lights similar to a traffic signal [72].
As is already known from other studies, various environmental and building-related factors, (for example the difference between outside and inside temperature, the wind speed and direction, the arrangement/orientation of the windows, etc.) influence the efficiency of NV [22,50,74]. Due to the heterogeneity of the studies identified in our literature search, it was not possible to derive general recommendations about such environmental and building-related factors. Korsavi et al. suggest designers be aware of all contextual, occupant, and building-related factors and consider, for example, that an opening can have different airflow rates depending on the season and the outdoor conditions [75]. With NV, cross ventilation should be used, which is more effective than single-sided ventilation [55]. This is also recommended by Ferrari et al. [71] and was shown by Aguilar et al. to be true of university classrooms [76].
The use of (portable) air purifiers (APs) was controversial. The literature search turned up three studies which examined the influence of APs on aerosol concentration [44,50,77]. The endpoint "aerosol concentration" did not meet the inclusion criteria, thus these studies were not listed in Table 2 unless the CO 2 concentration was also examined. In the three studies mentioned above, it was shown that it was possible to reduce the concentration of aerosol that could contain virus particles by means of air APs. It should be noted that these APs were equipped with HEPA filters. Air purification efficiency depends on, amongst others, the air purifier and filter class used. If it is not possible to guarantee the necessary air flow rates by means of MV or NV alone, an AP might be an ancillary measure for reducing the risk of infection. However, it should be kept in mind that APs only filter and recirculate air. Moreover, it is difficult to measure the effect of the air filtration during school hours. Although it is possible to conduct particle measurements, there are confounding factors, such as other sources of particles which are not emitted exclusively by human respiration which can influence the measurements. To guarantee good indoor air quality, the removal of "used air" and a supplementary supply of fresh outside air is still necessary to eliminate other (harmful) substances such as CO 2 and other gaseous contaminants like volatile organic compounds.
Improving the ventilation situation can also have side effects. Frequent and long NV periods can cause a significant drop in interior temperatures, particularly in winter months, and thus result in thermal discomfort for those present [24,36]. Other side effects of NV may include noise and air pollution from neighboring streets or construction sites [48].
In addition to eliminating potentially infectious aerosols, the viral emission of individuals should be kept as low as possible. This depends on, among other things, the age, the intensity with which an individual speaks, and the type of activity of the individuals. In general, especially with the wild type of SARS-CoV-2, adults have higher viral emission than children do and in the context of schools, mainly the teacher speaks a lot and loudly [12,[78][79][80][81][82][83]. The risk of transmission from teacher to student was greater than from student to teacher or from student to student in the studies identified [30,58]. The location of an infectious individual in the classroom can also influence the risk of infection. For example, the risk of inhaling a higher concentration of a pathogen was higher in close vicinity to the source individual, while the risk of infection decreased with increased distance from the infectious person [84][85][86]. For these reasons, we recommend that the distance between the teacher and the first row of school benches, in particular, should be large enough (at least 1.5 m) to reduce as much as possible the risk of infection to those in the near field of the teacher. Distance between students may further reduce the risk of infection, but due to limited classroom sizes, a large distance will not be possible in most classrooms. Since the teacher speaks the most and the loudest, the use of a microphone by the teacher can reduce the intensity of speech [22,61]. Other outbreak analyses have shown that transmission from teacher to teacher or from teacher to student had a large impact on outbreaks [52,87,88]. Likewise, Fleischer et al. postulate that particle emission by children is lower than by adults, possibly resulting in a lower risk of transmission by children. However individual/interpersonal variability of emission rates should be taken into consideration [79].
Improving ventilation can also reduce the transmission of other airborne pathogens. Du et al. (2020), for example, studied the impact of increased ventilation on tuberculosis outbreaks in poorly ventilated universities. As a result, maximum CO 2 concentrations were reduced from approximately 3200 ppm to concentrations of approximately 600 ppm, and the incidence of tuberculosis in contact individuals was reduced by 97%. In summary, guaranteeing that CO 2 concentrations do not exceed 1000 ppm could effectively control a tuberculosis outbreak in a university building [89].

Limitations
This review has several limitations. The number of intervention studies identified was small. Only studies published on or before 30 April 2022 were considered. Further studies have been published in the meantime which were not part of the review, with the exception of one that was highly relevant to this review. Similarly, other studies might have been found by expanding the keywords used in the literature search. In addition, we excluded observational and modeling studies published before 2020 whose primary endpoint was CO 2 concentration unrelated to the transmission of airborne infections. The same applies to the exclusion of studies conducted in low-income countries in climate zones unlike Germany's. Studies carried out in university classrooms were excluded due to room sizes, which are usually larger than school classrooms. Some results of such studies, however, might be applicable to school classrooms. CO 2 concentration was chosen as a primary endpoint because it is often used as a surrogate parameter for estimating the risk of infection. It needs to be evaluated whether other parameters might be more appropriate (e.g., CO 2 dose, relative humidity, temperature, etc.). Some of the study results were based on mathematical models whose estimates (e.g., the existence of a steady state or an even particle distribution in rooms) as well as specific values (e.g., quanta emission rate) were based on available data. The application of such models based on data of the wild type or early variants of SARS-CoV-2 to the current situation might be limited, as a result of the emergence of new SARS-CoV-2 variants and subsequent other individual emission rates and susceptibility. Our focus was on ventilation strategies as part of infection prevention measures. Hence, other measures, such as masks, regular screening tests, etc. were not discussed.

Conclusions
The ventilation situation in many schools is not adequate to guarantee good indoor air quality. Ventilation is an important measure for reducing the risk of airborne infection in schools. It is most important to reduce the time of residence of pathogens in the classrooms. Schools should have a well-functioning mechanical or natural ventilation system in order to avoid airborne infections in general. Compliance with ventilation measures must be ensured, in particular during a pandemic, and ventilation measures may need to be intensified to further reduce risk of infection during school operations.

Conflicts of Interest:
The authors declare no conflict of interest.